Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
52.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor starting point:
NOAEL
Value:
450 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
793 mg/m³
Explanation for the modification of the dose descriptor starting point:

In a GLP compliant OECD 407 study, the test material shows a NOAEL value of 450 mg/kg bw. This value was considerd as initial dose descriptor to derive the DNEL inhalative worker using standard procedure as described in the ECHA guidance.

First, the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m3 /kg for 8 hours exposure of workers, see Table R. 8 -2 in Section R.8.4.2). For workers (70 kg) the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 for basal level, 10 m3 for light activity).

NAEC = 450 mg/kg / 0.38 kg/m3 x 6.7 m3 / 10 m3 = 793 mg/m3

Using this approach results in a NAEC (worker) of 793 mg/m3.

AF for dose response relationship:
1
Justification:
clear dose response relationship was established in repeat dose studies
AF for differences in duration of exposure:
6
Justification:
Standard factor 28d - 2y
AF for interspecies differences (allometric scaling):
1
Justification:
Standard factors were considered in modification of point of departure.
AF for other interspecies differences:
2.5
Justification:
Standard factor ECHA considered for remaining differences, i.e. toxicokinetic differences not related to metabolic rate
AF for intraspecies differences:
1
Justification:
Standard factor worker was considered in modification of point of departure.
AF for the quality of the whole database:
1
Justification:
NO(A)EL was considered
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
450 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of starting point was considered, although much lower systemic bioavailability after dermal exposure can be assumed. Thus taking the oral NOAEL into account provides a clear worst case scenario.

AF for dose response relationship:
1
Justification:
clear dose response relationship was established in repeat dose studies
AF for differences in duration of exposure:
6
Justification:
Standard factor 28d - 2y
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor rat-human
AF for other interspecies differences:
2.5
Justification:
Standard factor ECHA considered for remaining differences, i.e. toxicokinetic differences not related to metabolic rate
AF for intraspecies differences:
5
Justification:
Standard factor worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population